The alkylation of C—H acidic compounds is a standard reaction of organic chemistry. One problem encountered in carrying out this reaction is that it is difficult to suppress dialkylation reactions. This is because, especially with strongly C—H acidic compounds, the acidity of the monoalkyl derivative is usually sufficient to promote further reaction with an electrophile. Since the singly and doubly alkylated derivatives are often difficult to separate, this can be a problem in situations where a high degree of selectivity is required (Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin, p. 517, 1986).
Previously described methods for the alkylation of strongly C—H acidic compounds, such as malonic esters or nitriles of malonic esters, have used sodium ethanolate or sodium hydride to produce deprotonated derivatives. These are subsequently trapped with an electrophile, for example an alkyl halide, in a substitution reaction (DE 3401913; EP 69648). There have also been attempts to use potassium carbonate as the base for alkylating malonic esters (Synth. Commun. 7:559–568 (1977); Zh Org. Khim. 19:474–480 (1983); DE 4326917). Although the references disclosing these procedures were primarily concerned with dialkylating malonic ester derivatives with 1,2-dihalogen alkanes to form cyclopropyl derivatives, the monoalkylation of malonic esters has also been disclosed. DE 19752041 describes a monoalkylation reaction which utilizes a molar ratio of malonic acidic derivative to alkylating agent to potassium carbonate of 1:1.5–3.0:0.4–0.6. The reference proposes that dialkylation may be accomplished by using quantity of base greater than or equal to 1 in relation to the C—H acidic compound.